The broad objective of this project is to understand the biology of the glycoprotein hormones, thyrotropin, luteinizing hormone, follicle stimulating hormone, and chorionic gonadotropin. Development of an extremely sensitive radioimmunoassay for chorionic gonadotropin in urine has facilitated the management of patients with neoplasms which secrete this marker. In addition, with this assay evidence has been obtained indicating that normal subjects excrete an hCG-like substance in urine. Studies of the metabolic clearance rates of the hCG subunits have shown that they have similar apparent initial volumes of distribution, but that the alpha subunit has much shorter half-lives than beta in both the rapid and slow phases to account for its more rapid clearance rate. MOre direct evidence that hCG interacts with the thyrotopin membrane receptor has been obtained. Future emphasis of the project will be on renal excretion and other mechanisms of disposal of the glycoprotein hormones and on the nature and etiologies of structural and functional heterogeneity in these hormones.